The long-term goal of this project is to elucidate basic principles of chemosensory perception. It seeks to explain at the molecular and cellular level how chemosensory information is encoded. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis of chemosensory receptors and neurons, and of the functions that they perform. The project focuses on a family of 30 predicted chemosensory receptors, the IR20a clade, that are expressed in chemosensory neurons. The project considers a kind of chemical information that underlies one of the most ancient and fundamental of biological problems: how an animal recognizes a suitable mate of its own species. An understanding of the molecular and cellular basis of species recognition could lead to new means of controlling insects that transmit disease to humans. The first aim examines two ionotropic receptors that are expressed in male neurons that are activated in a species-specific manner. The receptors in one species will be genetically replaced by their counterparts from another. The effects of this switch will be analyzed to test hypotheses about the molecular basis of species recognition. The second aim considers another ionotropic receptor that may act in females as a detector of male cues. The role of this receptor and the neurons in which it is expressed will be analyzed in detail. The results may support a model in which these neurons act in a checkpoint: if they receive an appropriate cue, an acceptance signal is sent to the central nervous system. The third aim capitalizes on an opportunity to analyze the role of a greatly understudied chemosensory organ, the wing. Different neurons on the wing are activated by different chemosensory cues, and an ionotropic receptor has been found to be expressed in a subset of these chemosensory neurons. The role of this receptor and the neurons in which it is expressed will be examined to determine if they are sensitive to species-specific cues. The results could provide a major advance in our understanding of a chemosensory organ whose function has remained speculative for 35 years.